"The post synaptic density (PSD) at excitatory glutamatergic synapses is a complex molecular machine which appears to be a key site of information storage. New methods to probe its structure show that a lattice-like backbone labeling for PSD-95 forms its core, while other structural components-synGAP, certain spectrin isoforms, SHANK, and the kinase CaMKII-occupy various locations at the lattice (but not all components of the PSD faction localize at PSDs). The total mass of the PSD measured by electron scattering from freeze-dried PSDs is 1-2 billion Da. The PSDs in intact neurons, however, change size rapidly during activity and these changes are rapidly reversible. Immunolabeling shows that CaMKII is a major component of the added mass. Furthermore, CaMKII at the PSD is in the phosphorylated from and reversibility is inhibited by specific phosphatases, suggesting that addition of CaMKII depends on phosphorylation. Measurements of the mass of PSDs from ischemic brains shows an increase in mass sufficient to allow for the addition of up to 500 CaMKII holoenzymes. A method has been developed to purify PSDs from other components of the PSD fraction, which will allow independent measurement of CaMKII content."